Leonardo Barcelos de Paula

[Human papillomavirus and public health: cervical cancer prevention].

The present study aimed to evaluate the applicability of an educational booklet that contained information for the general population about promotion and prevention of infections and neoplasic process caused by the human papillomavirus (HPV). The study was arranged in two phases. First, the booklet was given to 200 volunteers in the city of Goiânia, Goiás State. The applicability of the booklet was evaluated without the necessity of proving former knowledge. In the second phase, a detailed analysis of the data was made and the booklet revealed applicable. Then, the educational material was published and 2000 copies were distributed in a social event held by the Pontifícia Universidade Católica de Góias in the city of Goiânia. In the event, the booklet raised the interest of the general public and gave the volunteers a chance to participate in a study that investigated the presence of the HPV in the genital microbiote. The booklet proved to be applicable and reached its objective to inform and prevent. However, its necessary to promote and improve campaigns to the population about the HPV and its relations with the neoplasic process.

Aspectos clínico-epidemiológicos associados ao câncer de pênis

The general objective of this article is to review the current literature regarding the epidemiology, biological behavior and risk factors for penile cancer development, such as HPV infection. Phimosis and chronic irritation related to poor hygiene are commonly associated with penile cancer, whereas neonatal circumcision reduces the relative risk for the disease. There is strong evidence that HPV types 16 and 18 are associated with penile carcinoma in as many as 50% of cases. Patients with penile lesions should undergo physical examination, which is often sufficient to diagnose and to define tumor stagging, as well as contributes to decision-making regarding therapeutical approaches and case management.

Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells

Nanotechnology development provides new strategies to treat cancer by integration of different treatment modalities in a single multifunctional nanoparticle. In this scenario, we applied the multifunctional Pluronic P123/F127 mixed micelles for Verteporfin-mediated photodynamic therapy in PC3 and MCF-7 cancer cells. Micelles functionalization aimed the targeted delivery by the insertion of biotin moiety on micelle surface and fluorescence image-based through rhodamine-B dye conjugation in the polymer chains. Multifunctional Pluronics formed spherical nanoparticulated micelles that efficiently encapsulated the photosensitizer Verteporfin maintaining its favorable photophysical properties. Lyophilized formulations were stable at least for 6months and readily reconstituted in aqueous media. The multifunctional micelles were stable in protein-rich media due to the dual Pluronic mixed micelles characteristic: high drug loading capacity provided by its micellar core and high kinetic stability due its biocompatible shell. Biotin surface functionalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhodamine B-tagged micelles allowed monitoring cellular uptake and intracellular distribution of the formulations. Confocal microscopy studies demonstrated a larger intracellular distribution of the formulation and photosensitizer, which could drive Verteporfin to act on multiple cell sites. Formulations were not toxic in the dark condition, but showed high Verteporfin-induced phototoxicity against both cancer cell lines at low drug and light doses. These results point Verteporfin-loaded multifunctional micelles as a promising tool to further developments in photodynamic therapy of cancer.

Nanomedicine associated with photodynamic therapy for glioblastoma treatment

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most recurrent and malignant astrocytic glioma found in adults. Biologically, GBMs are highly aggressive tumors that often show diffuse infiltration of the brain parenchyma, making complete surgical resection difficult. GBM is not curable with surgery alone because tumor cells typically invade the surrounding brain, rendering complete resection unsafe. Consequently, present-day therapy for malignant glioma remains a great challenge. The location of the invasive tumor cells presents several barriers to therapeutic delivery. The blood–brain barrier regulates the trafficking of molecules to and from the brain. While high-grade brain tumors contain some “leakiness” in their neovasculature, the mechanisms of GBM onset and progression remain largely unknown. Recent advances in the understanding of the signaling pathways that underlie GBM pathogenesis have led to the development of new therapeutic approaches targeting multiple oncogenic signaling aberrations associated with the GBM. Among these, drug delivery nanosystems have been produced to target therapeutic agents and improve their biodistribution and therapeutic index in the tumor. These systems mainly include polymer or lipid-based carriers such as liposomes, metal nanoparticles, polymeric nanospheres and nanocapsules, micelles, dendrimers, nanocrystals, and nanogold. Photodynamic therapy (PDT) is a promising treatment for a variety of oncological diseases. PDT is an efficient, simple, and versatile method that is based on a combination of a photosensitive drug and light (generally laser-diode or laser); these factors are separately relatively harmless but when used together in the presence of oxygen molecules, free radicals are produced that initiate a sequence of biological events, including phototoxicity, vascular damage, and immune responses. Photodynamic pathways activate a cascade of activities, including apoptotic and necrotic cell death in both the tumor and the neovasculature, leading to a permanent lesion and destruction of GBM cells that remain in the healthy tissue. Glioblastoma tumors differ at the molecular level. For example, gene amplification epidermal growth factor receptor and its receptor are more highly expressed in primary GBM than in secondary GBM. Despite these distinguishing features, both types of tumors (primary and secondary) arise as a result dysregulation of numerous intracellular signaling pathways and have standard features, such as increased cell proliferation, survival and resistance to apoptosis, and loss of adhesion and migration, and may show a high degree of invasiveness. PDT may promote significant tumor regression and extend the lifetime of patients who experience glioma progression.

DNA polymeric films as a support for cell growth as a new material for regenerative medicine: Compatibility and applicability.

Abstract DNA polymeric films (DNA‐PFs) are a promising drug delivery system (DDS) in modern medicine. In this study, we evaluated the growth behavior of oral squamous cell carcinoma (OSCC) cells on DNA‐PFs. The morphological, biochemical, and cytometric features of OSCC cell adhesion on DNA‐PFs were also assessed. An initial, temporary alteration in cell morphology was observed at early time points owing to the inhibition of cell attachment to the film, which then returned to a normal morphological state at later time points. MTT and resazurin assays showed a moderate reduction in cell viability related to increased DNA concentration in the DNA‐PFs. Flow cytometry studies showed low cytotoxicity of DNA‐PFs, with cell viabilities higher than 90% in all the DNA‐PFs tested. Flow cytometric cell cycle analysis also showed average cell cycle phase distributions at later time points, indicating that OSCC cell growth is maintained in the presence of DNA‐PFs. These results show high biocompatibility of DNA‐PFs and suggest their use in designing “dressing material,” where the DNA film acts as a support for cell growth, or with incorporation of active or photoactive compounds, which can induce tissue regeneration and are useful to treat many diseases, especially oral cancer. HighlightsOral squamous cell carcinoma cells were successfully grown on DNA polymeric films.DNA polymeric films were not toxic to the cells at low concentrations of DNA.DNA polymeric films are proposed to act as a support for cell growth.Results are relevant for designing drug delivery systems for photodynamic therapy.

A importância da tecnologia de amplificação de ácidos nucléicos para a detecção do vírus da hepatite C em bancos de sangue doi: http://dx.doi.org/10.5892/ruvrv.2012.101.313328

The HCV, agent of hepatitis C, a virus belonging to the genus Hepacivirus of the Flaviviridae family, having a genome comprising a single strand of RNA. HCV transmission occurs via parenteral, such as blood transfusion and blood products, hemophiliacs, intravenous drug users or inhaled, material cutting or piercing can be a vehicle transmitter. The possibility of sexual transmission is still an open question and the transmission is also low, being, however, it may be increased if the patient has strong viremia and/or co-infection with HIV. The diagnosis of hepatitis C is based on serological tests such as ELISA and RIBA and molecular biology techniques. The ELISA detects antibodies against the virus anti-HCV, if the result is indeterminate confirmatory tests must be used such as RIBA. To confirm the diagnosis, we use a qualitative PCR RNA-HCV, and quantitative tests are used to evaluate viral-load, and they are also used to monitor therapeutic response. The nucleic acid amplification technique (NAT) results in a change of conventional laboratory methods, therefore, is quick to identify the “immune gap” period, approximately 50 to 60 days after contamination resulting from 10 to 11 days. The need for incorporation of NAT in blood banks is due to its ability to reduce the immune window period between infection and disease was discovered, thereby increasing transfusion safety.